Methods For Delivering A Drug To A Patient While Preventing The Exposure Of A Foetus Or Other Contraindicated Individual To The Drug

ABSTRACT

Novel methods for delivering a drug to a patient while preventing the exposure of a foetus or other contraindicated individual to the drug. Embodiments are provided in which the involved prescribers, pharmacies and patients are registered in one or more computer databases. Embodiments are also provided in which registered patients receive counseling information concerning the risks attendant to foetal exposure to the drug. Male patients and female patients who are not pregnant may, in certain circumstances, receive the drug.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of Ser. No. 11/104,013, filed Apr.12, 2005, which is a continuation of Ser. No. 10/762,897, now U.S. Pat.No. 6,908,432, filed Jan. 22, 2004, which is a continuation of Ser. No.10/383,665, now U.S. Pat. No. 6,767,326, filed Mar. 7, 2003, which is acontinuation of Ser. No. 09/964,068, filed Sep. 26, 2001, now U.S. Pat.No. 6,561,976, which is a continuation of Ser. No. 09/479,682, filedJan. 7, 2000, now abandoned, which is a continuation of Ser. No.09/143,569, filed Aug. 28, 1998, now U.S. Pat. No. 6,045,501, theentirety of which is incorporated herein by reference.

FIELD OF THE INVENTION

The present invention relates to novel methods for delivering a drug toa patient. More particularly, the present invention relates to novelmethods for delivering a teratogenic or other potentially hazardous drugto a patient while preventing the exposure of a person, such as afoetus, to the drug when such exposure is contraindicated. The novelmethods permit the distribution to patients of drugs, particularlyteratogenic drugs, in ways wherein such distribution can or must becarefully monitored and controlled.

BACKGROUND OF THE INVENTION

Thalidomide is a drug which was first synthesized in Germany in 1957.Beginning in 1958, it was marketed in many countries for use as asedative, although it was never approved for use in the United States.After reports of serious birth defects, thalidomide was withdrawn fromall markets by 1962. However, during the years it was used, it was foundto be effective in treating erythema nodosum leprosum (ENL), a conditionof leprosy, and the U.S. Food and Drug Administration (FDA) has made thedrug available for this specific use via a program of the Public HealthService. More recently, investigators have found that thalidomide may beeffective in treating AIDS wasting and aphthous ulcers occurring in AIDSpatients. In addition, treatments for other diseases, such as a numberof serious diseases including cancers, inflammatory bowel diseases andBehcet's Disease, rheumatoid arthritis, and macular degeneration, arealso believed to be possible. The FDA has recently approved anapplication by Celgene Corporation, which is the assignee of the presentpatent application, to market thalidomide for the treatment of ENL. Themedical community anticipates that thalidomide will be used fortreatment of additional conditions and diseases, including those setforth above. However, due to the severe teratogenic risk of thalidomide,methods are needed to control the distribution of this drug so as topreclude administration to foetuses. Methods for distribution of otherpotentially hazardous drugs are also needed to guard against improperprovision to persons for whom such drug is contraindicated.

Previous methods for controlling the distribution of drugs have beendeveloped in connection with Accutane (isotretinoin). Accutane, which isa known teratogen, is a uniquely effective drug for the treatment ofsevere, recalcitrant, nodular acne. A pregnancy prevention program wasdeveloped, and the Slone Epidemiology Unit of Boston University designedand implemented a survey to evaluate these efforts. The surveyidentified relatively low rates of pregnancy during Accutane treatment,which suggests that such a program can be effective. With more thanabout 325,000 women enrolled to date in the Accutane survey, it is alsoclear that such a large-scale study can be conducted. However,enrollment in the Accutane survey is voluntary. Accordingly, assessingthe representativeness of the women who have been enrolled in the surveyhas been problematic, and it has been difficult to determine whether thesurvey results can be generalized to all female Accutane users.

Thus, improved methods are needed which are more representative of allusers of a particular drug, such as thalidomide, who obtain the involveddrug through lawful distribution channels. Also, because drug sharingmay frequently occur, such as among AIDS patients, which may result inplacing a foetus at risk, a program is needed which can be used toeducate men and women about the risk of teratogenic drugs, such asthalidomide. The present invention is directed to these, as well asother important ends.

SUMMARY OF THE INVENTION

The present invention is directed to methods for the delivery ofpotentially hazardous drugs, such as teratogenic drugs, to patients. Inone embodiment of the invention, there are provided methods fordelivering a teratogenic drug to patients in need of the drug whileavoiding the delivery of said drug to a foetus comprising:

a. registering in a computer readable storage medium prescribers who arequalified to prescribe said drug;

b. registering in said medium pharmacies to fill prescriptions for saiddrug;

c. registering said patients in said medium, including informationconcerning the ability of female patients to become pregnant and,optionally, the ability of male patients to impregnate females;

d. retrieving from said medium information identifying a subpopulationof said female patients who are capable of becoming pregnant and,optionally, male patients who are capable of impregnating females;

e. providing to the subpopulation, counseling information concerning therisks attendant to fetal exposure to said drug;

f. determining whether patients comprising said subpopulation arepregnant; and

g. in response to a determination of non-pregnancy for said patients,authorizing said registered pharmacies to fill prescriptions from saidregistered prescribers for said non-pregnant registered patients.

Another embodiment of the invention relates to methods for delivering apotentially hazardous drug to patients in need of the drug whileavoiding the delivery of said drug to persons for whom said drug iscontraindicated comprising:

a. registering in a computer readable storage medium prescribers who arequalified to prescribe said drug;

b. registering in said medium pharmacies to fill prescriptions for saiddrug;

c. registering said patients in said medium, including informationconcerning the likelihood of said patients having a condition whichcontraindicates exposure to the drug;

d. retrieving from said medium information identifying a subpopulationof said patients who have a condition which contraindicates exposure tothe drug;

e. providing to the subpopulation, counseling information concerning therisks attendant to exposure to said drug;

f. determining whether patients comprising said subpopulation have saidcondition; and

g. in response to a determination that said patients do not have saidcondition, authorizing said registered pharmacies to fill prescriptionsfrom said registered prescribers for said registered patients for whomsaid drug is not contraindicated.

The methods described herein provide advantageous and effective meansfor monitoring, controlling and authorizing the distribution of drugs topatients, particularly teratogenic drugs. The methods of the presentinvention include a variety of checks and controls which serve to limitunauthorized and possibly inappropriate distribution of the drug. In thecase of teratogenic drugs, the checks and balances may be particularlyadvantageous for preventing distribution of the drug to patients whoseuse of the drug may pose an unacceptable risk of foetal exposure.Accordingly, the present methods may be advantageously used to avoidexposure of foetuses to teratogenic drugs, thereby avoiding the terriblebirth defects which may result from such exposure.

The invention is not limited to the distribution of teratogenic drugs;other potentially hazardous drugs may also be distributed in accordancewith embodiments of this invention and such drugs may be distributed insuch a fashion that persons for whom such drugs are contraindicated willnot receive them. These and other aspects of the invention will becomemore apparent from the present description and claims.

DETAILED DESCRIPTION OF ILLUSTRATIVE EMBODIMENTS

The present invention is directed generally to methods for the deliveryof drugs, especially teratogenic drugs, to patients. The term “drug,” asused herein, refers to any substance which is intended for use in thediagnosis, cure, mitigation, treatment or prevention of disease, or toaffect the structure or function of the body. Generally speaking, themethods of the present invention may be desirably and advantageouslyused to educate and reinforce the actions and behaviors of patients whoare taking the drug, as well as prescribers who prescribe the drug andpharmacies which dispense the drug. Such education and reinforcement ofactions and behavior are often necessary to ensure proper prescribingand dispensing of the drug, as well as patient compliance with takingthe drug. A wide variety of educational materials may be employed toensure proper prescribing, dispensing and patient compliance accordingto the methods described herein, including, for example, a variety ofliterature and other materials, such as, for example, productinformation, educational brochures, continuing education monographs,videotapes and the like which may describe the risks and benefitsassociated with taking the particular drug.

The methods described herein may be advantageously employed for thedelivery of a drug to a patient for whom the drug is contraindicated. Asused herein, the term “contraindicated” refers to any condition in apatient which renders a particular line of treatment, including theadministration of one or more drugs, undesirable or improper. Thus,contraindicated drugs include, for example, teratogenic drugs whoseadministration, for example, to pregnant patients is importantly avoideddue to the risks to the foetus. The methods of the present invention areespecially advantageously employed for the delivery to a patient of ateratogenic drug. The delivery of a teratogenic drug to a patient may beadvantageously achieved with the present methods while substantially(including completely) avoiding the delivery of the drug to a foetus(i.e., fetus). The term “substantially,” as used in reference toavoiding the delivery of a teratogenic drug to a foetus, generally meansthat there is an avoidance rate of delivering the drug to a foetus ofgreater than about 50%. Preferably, the avoidance rate is greater thanabout 55%, with an avoidance rate of greater than about 60% being morepreferred. Even more preferably, the avoidance rate is greater thanabout 65%, with an avoidance rate of greater than about 70% being stillmore preferred. Yet more preferably, the avoidance rate is greater thanabout 75%, with an avoidance rate of greater than about 80% being stillmore preferred. In even more preferred embodiments, the avoidance rateis greater than about 85%, with an avoidance rate of greater than about90% being yet more preferred. Still more preferably, the avoidance rateis greater than about 95%. In particularly preferred embodiments, ateratogenic drug may be delivered to patients with substantially nodelivery to foetuses (i.e., nearly 100% avoidance rate).

The drug delivery methods of the present invention preferably involve,inter alia, registering in a computer readable storage mediumprescribers who are qualified to prescribe the involved drug including,for example, teratogenic drugs. Once registered in the computer readablestorage medium, the prescriber may be eligible to prescribe the drug topatients in need of the drug. Generally speaking, in order to becomeregistered in the computer readable storage medium, the prescriber maybe required to comply with various aspects of the methods describedherein including, for example, providing patient education andcounseling, and the like, as described in detail below. The registrationof the prescriber in the computer readable storage medium may beachieved by providing the prescriber, for example, by mail, facsimiletransmission, or on-line transmission, with a registration card or form,preferably together with appropriate educational materials concerning,for example, the particular drug for which the prescriber is beingregistered to prescribe, as well as suitable methods for delivering thedrug to the patient, including the drug delivery methods describedherein. The prescriber will preferably complete the registration card orform by providing information requested therein, and the registrationcard or form will preferably be returned to the manufacturer ordistributor of the drug, or other authorized recipient of theregistration materials, for example, by mail, facsimile transmission oron-line transmission. Information which may be requested of theprescriber in the registration card or form may include, for example,the prescriber's name, address, and affiliation, if any, with one ormore health care institutions. The prescriber's information in theregistration card or form is then entered into the computer readablestorage medium. It is contemplated that the registration of theprescriber into the computer readable storage medium may also beachieved, for example, by telephone. Suitable computer readable storagemedia which may be employed for registration of the prescribers (as wellas the pharmacies and patients, as discussed below) will be apparent toone of ordinary skill in the art, once armed with the teachings of thepresent application.

In accordance with the methods described herein, pharmacies who arequalified to fill prescriptions for the particular drug being prescribedincluding, for example, teratogenic drugs, are also preferablyregistered in a computer readable storage medium. The computer readablestorage medium in which the pharmacies are registered may be the sameas, or different from the computer readable storage medium in which theprescribers are registered. Once registered in the computer readablestorage medium, the pharmacies may be eligible to dispense the involveddrug to patients who are in need of the drug. Generally speaking, inorder to become registered in the computer readable storage medium, thepharmacist may be required to comply with various aspects of the methodsdescribed herein including, for example, registering the patient(preferably also in a computer readable storage medium), as well asother aspects of the present methods, as described in detail below. Aswith the registration of the prescriber in the computer readable storagemedium, the registration of the pharmacy may be achieved by providingthe pharmacy, for example, by mail, facsimile transmission, or on-linetransmission, with a registration card or form, preferably together withappropriate educational materials concerning, for example, theparticular drug for which the pharmacy is being registered to dispense,as well as suitable methods for delivering the drug to the patient,including the drug delivery methods described herein. The pharmacy maythen have the registration card or form by providing the informationrequested therein, which thereafter may be returned to the manufactureror distributor of the drug, or other authorized recipient of theregistration card or form, for example, by mail, facsimile transmissionor on-line transmission. Information which may be requested of thepharmacy in the registration card or form may include, for example, thepharmacy's name, address, and affiliation, if any, with any health careinstitution such as, for example, a hospital, pharmacy, and the like.The pharmacy's information in the registration card or form is thenpreferably entered into the computer readable storage medium. It iscontemplated that the registration of the pharmacy into the computerreadable storage medium may also be achieved, for example, by telephone.

As noted above, the drug delivery methods described herein alsopreferably involve the registration of the patient in a computerreadable storage medium. As discussed below, the registration of thepatient is preferably carried out by the registered pharmacy at the timeof the patient's initial visit to the pharmacy. The computer readablestorage medium in which the patients are registered may be the same as,or different from the computer readable storage medium in which theprescriber and/or pharmacy is registered. Once registered in thecomputer readable storage medium, the patient in need of a particulardrug including, for example, a particular teratogenic drug, may beeligible to receive the drug. Generally speaking, in order to becomeregistered in the computer readable storage medium, the patient may berequired to comply with various aspects of the methods described herein.In preferred form, the pharmacy will typically have a registration formfilled out for the patient, which includes information on the patient,such as the patient's name, mailing address, date of birth, and thelike. Information on the prescribing prescriber and dispensing pharmacy,such as the information described above for the registration thereof,may also be desirably entered on the patient registration form. Thecompleted form may then be forwarded to the manufacturer or distributorof the drug, or other authorized recipient of the registration form, forexample, by mail, facsimile transmission or on-line transmission. It iscontemplated that the registration of the patient into the computerreadable storage medium may also be achieved, for example, by telephone.

In accordance with the methods of the present invention, the delivery ofthe drug to the patient may involve the following steps. As a prelude toprescribing and dispensing the drug to the patient, the prescriber andthe pharmacy are registered in one or more appropriate computer readablestorage media, as described above. If the prescriber is not registeredin the computer readable storage medium, the prescriber will beineligible to prescribe the drug. Similarly, if the pharmacy is notregistered in the computer readable storage medium, the pharmacy will beineligible to dispense the drug.

In the course of an examination of a patient, including patientssuffering from one or more diseases and/or disorders such as, forexample, erythema nodosum leprosum (ENL), the prescriber may determinethat the patient's condition would be improved by the administration ofa drug such as, for example, a teratogenic drug, including thalidomide.Prior to prescribing the drug, the prescriber preferably counsels thepatient, for example, on the various risks and benefits associated withthe drug. For example, the prescriber preferably discusses the benefitsassociated with taking the drug, while also advising the patient on thevarious side effects associated therewith. Thus, a patient who mayacquire or impart a condition or disease for which the drug iscontraindicated is preferably counseled by the prescriber on the dangersassociated therewith. For example, in the case of teratogenic drugs, theprescriber preferably counsels the patient on the dangers of exposing afoetus to the teratogenic drug. Such counsel may be provided verbally,as well as in written form. In preferred embodiments, the prescriberprovides the patient with literature materials on the drug for which aprescription is contemplated, such as product information, educationalbrochures, patent instruction videos, and the like. Thus, in the case ofmethods involving teratogenic drugs, the prescriber preferably providespatients with literature information, for example, in the form of theaforesaid product information, educational brochures, patent instructionvideos, and the like, warning the patient of the effects of the drug onfoetuses.

With particular reference to counseling provided in connection withteratogenic drugs, the prescriber preferably counsels female patientsthat such drugs must never be used by pregnant women. If the patient isa female of child-bearing potential (i.e., a woman who is capable ofbecoming pregnant), the prescriber preferably counsels the patient thateven a single dosage of certain teratogenic drugs, such as thalidomide,may cause birth defects. Accordingly, the patient is preferablycounseled to avoid sexual intercourse entirely, or if sexually active,to use appropriate forms of contraception or birth control. For bothmale and female patients, the prescriber preferably provides counsel onthe importance of using at least two forms of effective birth controlmethods, with one form being a highly effective hormonal method, and theother form preferably being an effective barrier method. The patientsare preferably counseled to use the birth control methods for a periodof time prior to enduring treatment with the teratogenic drug, as wellas for a period of time after treatment with the drug has beenterminated. In preferred embodiments, the patient is counseled to use atleast two forms of birth control for at least about 4 weeks prior toinitiation of treatment, during treatment, and for at least about 4weeks after treatment has been terminated. It may be desirable for theprescriber to personally provide female patients who are capable ofbecoming pregnant with a contraceptive device or formulation.

Male patients who are being prescribed a teratogenic drug are preferablycounseled to use condoms every time they engage in sexual relations,since many teratogenic drugs may be found in semen. Male patients arealso preferably counseled to contact their prescriber if they havesexual intercourse without a condom, and/or if it is believed that theymay have caused a pregnancy. As with female patients, it may bedesirable for the prescriber to provide male patients who are capable ofimpregnating female patients with a contraceptive device or formulation.Other advice relative to birth control that the prescriber may provideto the patient would be apparent to one skilled in the art, once armedwith the teachings of the present application. If the prescriber who isprescribing the teratogenic drug is unaware of certain aspects of theavailable forms of birth control and the advantages and disadvantagesassociated therewith, the patient should be referred to a prescriber whois knowledgeable on such matters, prior to be being prescribed theinvolved drug. Generally speaking, as discussed below, counseling onteratogenecity, birth control, and the like is preferably given only tofemale patients who are capable of becoming pregnant, or to malepatients who are capable of impregnating female patients. In thismanner, unnecessary counseling, for example, to women who are no longerof child-bearing age or men who are incapable of impregnating women, maybe avoided.

With further reference to methods involving teratogenic drugs, it isalso preferred that the prescriber advise the patient to not share thedrug with anyone else, and particularly that the drug should be kept outof the reach of children as well as women of child-bearing potential. Inthe case of female patients, particularly female patients ofchild-bearing potential, the prescriber should give the patient apregnancy test, preferably a serum pregnancy test, prior to and duringtreatment with the teratogenic drug. To begin receiving the teratogenicdrug and to continue taking the drug, female patients of child-bearingpotential should continue to have negative pregnancy tests. The patientis also preferably counseled by the prescriber to discard or return tothe prescriber, pharmacy, manufacturer or distributor any unused portionof the prescribed drug.

As would be apparent to one of ordinary skill in the art, once armedwith the teachings of the present application, one or more aspects ofthe counseling described above may be applicable, in certaincircumstances, for drugs other than teratogenic drugs.

In addition to receiving counseling on the drug being prescribed,including counseling, for example, on birth control, and prior toreceiving a prescription for the drug, the methods of the presentinvention preferably involve requiring the patient to fill out aninformed consent form which is signed by the prescriber, as well as thepatient. The prescriber should retain a copy of the informed consentform for his/her records. By filling out and signing an informed consentform, the patient acknowledges that he/she understands the risksassociated with taking the drug. In the informed consent form, thepatient preferably agrees to behave in a manner which is consistent withthe prescriber's counsel. For example, in cases involving, for example,teratogenic drugs, the patient may agree to use at least one form ofbirth control, with female patients agreeing to use at least two formsof birth control. In preferred embodiments involving teratogenic drugs,female patients preferably agree also to undergo pregnancy testing,preferably serum pregnancy testing, before, during and after treatmentwith the teratogenic drug. Female patients preferably will alsoacknowledge that, at the time they are being prescribed the drug,especially teratogenic drugs, they are not pregnant, they willimmediately stop taking the drug if they become pregnant, and they willnot try to become pregnant for at least 4 weeks after treatment with thedrug is terminated. Female patients, especially female patients for whoma teratogenic drug will be administered, preferably further agree tocontact their prescriber if they wish to change one or more of the birthcontrol methods being used and to have an additional pregnancy test if amenstrual period is missed. Female patients, especially female patientsto be treated with teratogenic drugs, will preferably agree also to notbreast-feed while being treated with the drug.

Male patients who are being prescribed the drugs according to themethods described herein, especially teratogenic drugs, will preferablyagree to avoid having unprotected sexual relations with a woman,particularly a woman of child-bearing potential during treatment withthe drug. In doing so, male patients will preferably further agree touse a condom during sexual relations with a woman, with latex condomsbeing preferred. Both male and female patients will also preferablyagree to not share the drug with anyone, and to acknowledge that theycannot donate blood while taking the drug, with male patients agreeingalso to not donate sperm while taking the drug. In addition, thepatients will preferably agree to take part in a confidential patientsurvey, for example, before, during and after treatment with the drug.The patient survey provides information, for example, to the prescriber,manufacturer and/or distributor of the drug, as well as any group orbody which may be established to generally provide oversight on thedistribution of the drug, on information regarding the general lifestyleof the patient, including detailed information on the patient's sexualbehavior. In this manner, the survey may assist in identifying patientswho engage in risky behavior, as well as patients who are non-compliantwith the methods described herein. Such risky behavior and/ornon-compliance may lead to a suspension or intervention of the patient'streatment with the drug, with re-education being provided to thepatient.

The information obtained from the survey is preferably also entered intothe computer readable storage medium. Once entered into the computerreadable storage medium, the prescriber, manufacturer and/or distributorof the drug may be able to glean therefrom information regarding thelevel of risk associated with the administration of the involved drug tothe various patients. Accordingly, it may be possible to identify, fromamong the entire population of registered patients, one or moresubpopulations of patients for which the involved drug may be morelikely to be contraindicated. For example, it may be possible toidentify a subpopulation of female patients who are capable of becomingpregnant and/or a subpopulation of male patients who are capable ofimpregnating female patients. Preferably, the counseling informationdiscussed above relating to exposure of a foetus to a teratogenic drugmay then be addressed primarily to this subpopulation of patients.

If the risk is considered to be acceptable, the patient may continue toreceive the drug, using the methods described herein. If the risk isconsidered to be unacceptable, additional counseling may be provided tothe patient or, if necessary, treatment of the patient with the involveddrug may be terminated, with alternate treatment modalities beingprovided. In preferred embodiments, female patients will agree tocomplete a patient survey at least once every month, with male patientsagreeing to complete a patient survey at least once every three months.

After the patient has received counseling as described above, and hasalso filled out and signed an informed consent form, and it isdetermined that the drug which is to be prescribed is notcontraindicated for the patient (such as, for example, a negativepregnancy test in the case of female patients for whom a prescription isdesired for a teratogenic drug), the prescriber may prescribe the drugto the patient. In preferred embodiments of the present invention, theamount of the drug which is prescribed to the patient is for a limitedamount, preferably no more than about 28 days. Refills for the drug willnot be permitted without a renewal prescription from the prescriber, asdiscussed in detail below. In order to have the prescription filled, thepatient preferably presents the prescription and the informed consentform to a pharmacy which has been registered, as discussed above. It iscontemplated that the patient may bring the prescription to anunregistered pharmacy. If so, the pharmacy may take steps to becomeregistered, for example, by immediately contacting the manufacturer ofthe drug. Once registration of the pharmacy is completed, thedistribution procedure described herein may resume, per the discussionhereinafter. Of course, this may introduce a delay into the prescriptionprocess, and the patient may desire to take the prescription for thedrug to an alternate, registered pharmacy. If the patient does notpresent a completed informed consent form to the pharmacy, theprescription may not be filled. In this case, pharmacy may contact theprescribing prescriber to have an informed consent form filled out forthe patient.

Prior to filling out the prescription and dispensing the drug, theregistered pharmacy preferably has a patient registration form filledout for the patient, and the patient is registered in an appropriatecomputer readable storage medium. The pharmacy may then dispense thedrug to the patient. A copy of the patient's informed consent formshould be kept for the pharmacy's records. The drug is preferablysupplied to the pharmacy (as well as the patient) in packaging, such asindividual blister packs, which includes warnings regarding the risksassociated with the drug, as well as the importance of various aspectsof the present methods such as, for example, pregnancy testing and theuse of contraception (in the case of teratogenic drugs), and the dangersassociated with sharing the drug with others, among other aspects.

As noted above, the drug is preferably prescribed and dispensed to thepatient in a limited amount, with a prescription amount of no more thanabout 28 days being preferred, and preferably with no refills beingpermitted. Thus, for the patient to obtain an additional prescription,it is generally necessary for the patient to have a follow-up visit withthe prescriber. Such a follow-up visit preferably takes place at leasteach time the patient requires a renewal of the prescription, andpossibly more often if the patient requires, for example, additionalcounseling. At the follow-up visit, the patient will preferably receiveadditional counseling regarding the risks and benefits associated withtaking the drug, as well as further counseling on birth control (ifapplicable). The patient will also preferably complete an additionalpatient survey to provide current information regarding their lifestyle,including their sexual behavior and, if female of childbearingpotential, be administered a new pregnancy test. After receiving thecounseling and completing the patient survey, and if the pregnancy testsfor female patients are negative, the prescriber may fill out a newprescription for the drug. As with the original prescription, therenewal prescription is preferably for a limited period of time, with nomore than about 28 days being more preferred.

In preferred embodiments, the prescriber will also receive reminders,for example, via mail, facsimile, or on-line transmission, from themanufacturer, distributor or other group or body providing oversight ondrug distribution, that the prescriber has prescribed a hazardous drugto patients which may be contraindicated, and that the involved patientsmay require additional counseling and pregnancy testing. Such remindersmay preferably be delivered to the prescriber, for example, from about14 to about 21 days after the previous prescription was filled.

As with the original prescription from the prescriber, the patientshould present all renewal prescriptions to a registered pharmacy. Priorto filling out the prescription and dispensing the drug, the pharmacypreferably confirms, for example, via a standard on-line transmission orvia telephone, that the patient has been registered and is eligible toreceive the drug. When patient eligibility has been confirmed, thepharmacy may dispense the drug to the patient. If the patient isineligible, the pharmacy generally may not dispense the drug to thepatient. The pharmacy may then contact, for example, the prescribingprescriber or the manufacturer of the drug to initiate patientregistration. In preferred form, the pharmacy will be precluded fromdispensing the drug if the patient has more than about 7 days of drugsupply from the previous prescription, and/or if the new prescriptionwas written more than about 14 days before the date the patient visitsthe pharmacy to have it filled.

The registration into one or more computer readable storage media of theprescriber, pharmacy and patient, according to the methods describedherein, provide a means to monitor and authorize distribution ofcontraindicated drugs, including teratogenic drugs. Thus, the computerreadable storage media may serve to deny access, dispension orprescriptions of contraindicated drugs, including teratogenic drugs, topatients, pharmacies or prescribers or fail to abide by the methods ofthe present invention. As noted above, prescribers who are notregistered in a computer readable storage medium generally may notprescribe the drug, and pharmacies who are not registered generally maynot dispense the drug. Similarly, the drugs generally may not beprescribed and/or dispensed to patients who are not registered in acomputer readable storage medium. In addition, patients are alsogenerally required to present an informed consent form to the pharmacy.Unless such a form is presented to the pharmacy, the patient generallymay not receive the prescription for the drug. As noted above, onlylimited amounts of the drug may be prescribed to the patient, with norefill prescriptions being permitted. The pharmacy may not receive moredrug for distribution unless he can account for all drug previouslydispensed. Also, the pharmacy may only continue to distribute the drugto registered patients who have prescriptions from registeredpharmacies.

Various modifications of the invention, in addition to those describedherein, will be apparent to those skilled in the art from the foregoingdescription. Such modifications are also intended to fall within thescope of the appended claims.

1. A method of treating a male patient having a disease or conditionresponsive to a teratogenic drug comprising (A) permitting the drug tobe distributed by a pharmacy only after the pharmacy has received aprescription and (B) administering the drug to the patient, wherein thegeneration of the prescription comprises the following steps: (a) via acomputer readable storage medium, registering a prescriber and thepharmacy with a distributor of thalidomide; (b) determining whether thepatient is able to understand and carry out instructions; (c) upondetermination that the patient is able to carry out the instructions,providing verbal and written warnings of the hazard of taking the drugand exposing fetus to the drug; (d) further providing verbal and writtenwarnings of the risk of possible contraception failure and of the needto use barrier contraception when having sexual intercourse with womenof child bearing potential; (e) obtaining acknowledgement of saidwarnings from the patient; (f) via a computer readable storage medium,registering the patient with the distributor; and (g) upon obtaining theacknowledgement and registrations, generating via a computer readablestorage medium the prescription to be retrieved by the pharmacy beforethe drug is distributed.
 2. The method of claim 1, wherein theacknowledgement requires the patient's acknowledgement of one or more ofthe following: (a) the understanding that the drug must not be taken ifunprotected sex cannot be avoided; (b) the understanding of potentialbirth defects; (c) that the patient has been advised of the need forbarrier contraception by the prescriber; (d) the obligation to informthe prescriber if the patient's sexual partner is suspected of becomingor being pregnant; (e) that the drug is solely for the use of thepatient himself and must not be shared with any other person; (f) thatthe patient has read the information brochure or viewed the informationfilm on the drug; (g) that the semen or blood must not be donated duringthe drug treatment; (h) that all of the patient's inquiries regardingthe drug treatment have been answered by the prescribing physician; or(i) the patient's understanding that participation in a survey andpatient registry is required during the drug treatment.
 3. The method ofclaim 1 further comprising obtaining a written authorization by theprescriber.
 4. The method of claim 1, wherein the acknowledgement is awritten informed consent and wherein the pharmacy fills the prescriptiononly upon patient's presentation of the written informed consent to thepharmacy.